8 replies to this topic

[IndyX]

...as a part of pssd treatment? I did try some stuff, but going back to basics. Is that protocol still state-of-the-art?

 

http://area-1255.for...o-treating-pssd

 

I mean opiate antagonism/agonism. How about selective serotonin reuptake enhancing properties of Tianeptine?

 

I'm looking for some safe mood-lifter, which doesn't mess with serotonin system. Supposedly Tianeptine works through glutamate receptors, BDNF and stuff.

 

Going (among others) into 25mgs of Naltrexone at night and 3x12,5mgs of Tianeptine - wouldn't that combo fuc*k me further in the long term? Naltrexone is a must for me, I'm not sure about Tianeptine.

[PeaceAndProsperity]

I would love to try naloxone/naltrexone if I could get my damned hands on any of them in pharmaceutical grade without having to pay 100 dollars per pill/injection. For drugs that are so safe and used to treat opiate addiction and live safer and bla bla bla, it sure isn't easy to get one's hand on it.

 

https://en.wikipedia...i/Enkephalinase

https://en.wikipedia...inase_inhibitor

If you could find a drug that enhances Enkephalinase, you could get an opiate antagonist (to my knowledge).

D-phenylalanine, according to the above Wikipedia article, blocks the breakdown of opiate peptides via the blocking the enzyme which is responsible for the breakdown. Ironically, having tried D-phenylalamine, I've experienced it to have anti-apathy effects which is completely contradictory to what one would expect, though of course its anti-apathy effect is very mild and I've tried the DL-phenylalanine version, which could mean that it's actually l-phenylalanine having this effect.

If you find any opioid antagonists that are cheap, effective and (hopefully) legal, please post them as it would be a great contribution to me.

 

Other than giving a bump and the above information, I can't provide more to the topic.
 

 

[fntms]

They sell generic naltrexone on reliablerx, adc's sister site. They are... reliable...

[Area-1255]

OP - that is one article of ours, but this one is the main one. 

Insights into PSSD ~ A Collection of Data & Detailed Analysis of the Etiology and Pathology of Post-SSRI-Sexual Dysfunction as well as Possible Novel Treatment Approaches

 

It will take you a while to read it all - but that one contains the most collected information to date on the 'PSSD Issue'.

I even went over liver enzyme and glycoprotein alterations caused by the drugs and a host of other neurophysiological contributing factors...you'll want to read it, trust me.

 

As far as naltrexone; it's hit or miss for some people...it has it's benefits but it doesn't guarantee reinstatement of sexual function..one thing in particular you have to be aware off, is the inverse correlation between endorphins and sympathetic nervous system activity...essentially that means that if your problem is adrenaline related - as in too much adrenaline, opiate antagonists are most likely NOT going to help and may just make it worse...but , it also depends on other factors...

At the same time, many people with very high adrenaline also have tons of beta-endorphin flipping around ; the point is you then, have to target both; so something like an alpha-1-blocker plus opiate antagonist may be ideal; depending on if the issue is mainly with libido or arousal by vascular standpoint.

 

Tianeptine takes a few weeks to work in regards to boosting dopamine receptors, but it also has effects as an mu-opioid agonist; so traditionally I recommend using tianeptine plus phenyl piracetam and lavender for about 4-8 weeks THEN switching to the next phase; which may include working on the endorphin/dynorphin system..

 

As always, look at hormones first - they can give you a 'trend' as to what direction to go in... 

Free Testosterone will always be important as will it's ratio with estrogen and cortisol and prolactin as well. 

 

How to Prevent/Reverse Dopamine Receptor Downregulation from Dopamine Agonists, Stimulants and other Causes

Edited by Area-1255, 21 September 2015 - 09:35 PM.

[IndyX]

@Area-1255

 

I'd read it. Especially liked this part: Zoloft induced sexual dysfunction seems to be one of the worst. Yay, that's my pill.. Although can't say I comprehend everything at this very moment.

 

Still diggin..nevertheless:

 

25mgs of Naltrexone seems to be promising. Despite some insomnia, placebo or not, it felt right, doable and on its place.

 

So..according to my understanding, Tianeptine is supposed to rebuild some parts of my brain, thanks to its nootropic properties mediated via agonizing opioid receptors? 

http://www.nature.co.../tp201430a.html

 

Taken together, these results lead us to hypothesize that activation of MOR (or possibly dual activation of MOR and DOR) is the initial molecular event responsible for tianeptine’s modulation of the glutamatergic system and for triggering many of the known acute and chronic effects of this agent, including its antidepressant/anxiety actions.

 

So what is the difference between Tianeptine (forgive being stupid - blame SSRI's) and Low Dose Naltrexone and Naltrexone?

 

 

 

Naltrexone and its active metabolite 6β-naltrexol are antagonists at the μ-opioid receptor (MOR), the κ-opioid receptor (KOR) to a lesser extent, and to a far lesser extent, at the δ-opioid receptor (DOR).

 

Wouldn't it be more "natural" to use LDN instead of Tianeptine? Seems like messing with these opioid receptors jumpstarts some veiled cascade of beneficial neuroevents.

 

And exactly what kind advantage has 25mg over 4mg of Naltrexone?

 

@RatherBeUnknown Isn't it 100$ for 28 pills? PM me if you can't get that stuff.

 

[Area-1255]

 

 

25mgs of Naltrexone seems to be promising. Despite some insomnia, placebo or not, it felt right, doable and on its place.

 

So..according to my understanding, Tianeptine is supposed to rebuild some parts of my brain, thanks to its nootropic properties mediated via agonizing opioid receptors? 

http://www.nature.co.../tp201430a.html

Seems that way - but it also has to do with interactions with carrier proteins and glutamate systems

 

So what is the difference between Tianeptine (forgive being stupid - blame SSRI's) and Low Dose Naltrexone and Naltrexone? Tianeptine helps to raise dopamine receptors and regrowth of neurons - that's why you PRIME your recovery with that + PHENYL PIRACETAM FIRST...before naltrexone..

 

Wouldn't it be more "natural" to use LDN instead of Tianeptine? Seems like messing with these opioid receptors jumpstarts some veiled cascade of beneficial neuroevents.

 

And exactly what kind advantage has 25mg over 4mg of Naltrexone?

 

@RatherBeUnknown Isn't it 100$ for 28 pills? PM me if you can't get that stuff.

Using LDN at very low doses has more pronounced effects on beta-endorphin levels; it would simply skyrocket the level of endogenous opioid peptides - so this would further inhibit/decrease sexual desire - remember the whole point of sexual conquest or pleasure behind it in the first place is TO GET an endorphin rush - so if we already have tons floating around then we are in SATIETY mode..our brain tells us we don't need anything...so from a biological standpoint you want to antagonize the receptors enough to effectively DISINHIBIT dopaminergic/glutamatergic neurons. 

 

When remove the barriers/obstacles laying their path in front of dopamine and the inhibiting neurons connected to and from - then dopamine can exert it's interactions on libido and arousal...but as long as noradrenaline, serotonin or endorphins, or even endocannibinoids are floating around in excess - dopamine can't do it's work. 

[Geoffrey]

I would love to try naloxone/naltrexone if I could get my damned hands on any of them in pharmaceutical grade without having to pay 100 dollars per pill/injection.

But it's so easy and cheap to get hold of pharmaceutical naltrexone (Nodict)! Ten 50mg tablets for £13.99 from inhousepharmacy, for example, including shipping. Since your typical low-dose naltrexone regime has a maximum of 4.5mg per night, that 50mg tablet is going to last 11 doses, but probably longer because 4.5mg is the max. I've got a few strips of the stuff I was using for an inflammatory problem that the doctors couldn't find the cause of, and could only treat with steroids or NSAIDs.

I recently started experimenting with tianeptine for nootropic purposes (I haven't taken naltrexone for several weeks). I'm really enjoying the calming effect, the brightening of colours and the sense of all being "right" with the world. But I'm worried about possible small, but nevertheless tangible, opioid dependency and was wondering if I could use LDN at night as a way of resetting the opioid receptors, as well as ongoing treatment for my inflammation. The theory behind LDN is that it starves the receptors overnight by blockading them, causing a rebound the next day. I think 4.5mg would be too high, as last time I took that quantity, the ramp up of endorphins the next day at times made me dizzy. But maybe 1 or 2 mg might have the desired effect. I'm going to experiment and see how it lives alongside tianeptine. Will report back, but I'd be interested in any theoretical discussion of what the combination of these chemicals might do, or whether they are both trying to achieve the same effect through different mechanisms.

Edited by Geoffrey, 25 September 2015 - 08:41 PM.

[Area-1255]

 

I would love to try naloxone/naltrexone if I could get my damned hands on any of them in pharmaceutical grade without having to pay 100 dollars per pill/injection.

. The theory behind LDN is that it starves the receptors overnight by blockading them, causing a rebound the next day. 

That is correct - and thus beta-endorphin rises very high - which creates a relaxing effect on the nervous system and a mild mood boost..but this is well and fine if MOOD LIFTING is your goal; but high beta-endorphin is NOT want you want in terms of sex drive - which comes from SEEKING the endorphin rush and pleasure associated with sex and thus you need to adequately block the opioid-like systems that are DIRECTLY INHIBITING the reward-cycle --- now normally - under 'typical' circumstances - free testosterone and DHT would suppress serotonergic activity whilst estrogen antagonizes (in small - moderate amounts ONLY) the alpha-1 receptors channels and 5-HT1A / 1B receptors which then leads to increases in dopamine/glutamate in the hypothalamus/PVN.

 

When other things are involved though - and changes in reward circuitry are placed - then this becomes all messed up and serotonin or too much adrenaline causes too much endorphin/dynorphin..which is why norepinephrine and serotonin BOTH need to be low in order to have a normal libido..not SUPER low but lower than say, dopamine and histamine. and especially glutamate.

 

 

Psychoneuroendocrinology. 1989;14(1-2):103-11.

Endorphins in male impotence: evidence for naltrexone stimulation of erectile activity in patient therapy.

Fabbri A1, Jannini EA, Gnessi L, Moretti C, Ulisse S, Franzese A, Lazzari R, Fraioli F, Frajese G, Isidori A.

Author information

 

Abstract

In the present study we evaluated whether naltrexone administration could stimulate sexual function in 30 male patients, ages 25 to 50 years, with idiopathic impotence of at least one year's duration and not of organic etiology. The patients received naltrexone (50 mg/day) or placebo, on a random basis for two weeks. Sexual performance, expressed as the number of full coitus/week, was assessed before (time 0) and during (on days 7 and 15) each treatment. The naltrexone therapy significantly increased the number of successful coitus compared to placebo after 7 and 15 days of treatment: improvement of sexual performance was evident in 11 out of the 15 treated patients. All the patients experienced a significant increase in morning and spontaneous full penile erections/week. No significant side effects were reported. Endocrine studies revealed no significant modification of plasma LH, FSH or testosterone by naltrexone, suggesting that the positive effect of the drug on sexual behavior was exerted at a central level. A two-month follow-up, at which time patients were off treatment, erectile capacity had returned to baseline in 10 patients, while five reported complete recovery of their sexual ability. We hypothesize that an alteration in central opioid tone is present in idiopathic impotence and is involved in the impairment of sexual behavior.

PMID:   2543996   [PubMed - indexed for MEDLINE]

 

 

Inhibition of sexual behavior by dopamine antagonist or serotonin agonist drugs in castrated male rats given estradiol or dihydrotestosterone

Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

Pharmacology Biochemistry and Behavior (Impact Factor: 2.78). 07/1980; 13(1):57-67. DOI: 10.1016/0091-3057(80)90121-5

ABSTRACT Four experiments were performed to determine whether the activational effects of two behaviorally active neural metabolites of testosterone, estradiol (E2) and 5??-dihydrotestosterone (DHT), on male rats' sexual behavior possibly result from the action of either steroid at dopaminergic or serotoninergic synapses. In Experiment 1 lower doses of the dopamine receptor antagonist, spiperone, were needed significantly to reduce mounting and intromission rates in castrated males implanted with silastic capsules containing E2 as opposed to DHT. However, in Experiment 2 increasing doses of another dopamine receptor blocker, clozapine, were equally effective in suppressing males' sexual behavior, regardless of whether they were implanted with E2 or DHT, suggesting that these testosterone metabolites may both normally contribute to the activation of masculine sexual behavior by enhancing dopaminergic neurotransmission. In Experiment 3 administering increasing doses of the serotonin reuptake blocker, fluoxetine, caused an equal suppression of sexual behavior in castrated males implanted with E2 of DHT. In Experiment 4 no differential suppressive effects of the serotonin receptor agonist, 5 methoxy-N,N-dimethyltryptamine were obtained in castrated rats implanted with E2 or DHT. It is suggested that these testosterone metabolites may both contribute to the activation of masculine sexual behavior by suppressing activity at serotoninergic synapses.

Inhibition of sexual behavior by dopamine antagonist or serotonin agonist drugs in castrated male rats given estradiol or dihydrotestosterone - ResearchGate. Available from: http://www.researchg...drotestosterone [accessed Sep 25, 2015].

Edited by Area-1255, 25 September 2015 - 08:57 PM.

[Geoffrey]

I've continued to take LDN nearly every night since my last post in September (for a chronic inflammatory condition). I now take tianeptine on and off, for when I feel I need to be in a relaxed but sharp state, for example when giving a presentation or conducting a class.

 

What I found combining these two was that the LDN did seem to cancel out any tolerance to the opioid-like effects of tianeptine, but it also means that, if I try to dose tianeptine (sodium) at 3 x 10mg per day, it's far too easy to get into some kind of over-stimulated state where you can't think straight. It's a kind of brain fog combined with a paradoxical kind of "happy anxiety". That's the best I can do to describe the effect on me. I also get dry, itchy eyes and in the worst case, sometimes red itchy eyes on this combination if I try to dose it for more than a few days at a time. This means that I've had to stop using tianeptine daily, and reserve it for special cases where stress might otherwise be debilitating. I try not to take it more than twice a day (i.e. no more than two 10mg pills), and no more than two days in a row. I have to leave at least one day's gap between days on, though more is better.

 

I should add the caveat that my body seems quite bad at clearing psychoactive substances from my bloodstream, or from my brain. I seem to need much lower doses than those recommended for almost all nootropics of the racetam family, and I can't take piracetam at all without feeling horribly drained. Noopept, pramiracetam and oxiracetam are fine, in small doses, but they build up far too fast for me until they have paradoxical effects.

 

Ah, one more thing. I've found taking a small dose of noopept (about 4mg) before, or at the same time, as a tianeptine pill seems to attenuate or smooth out the euphoric effects which can often be unwanted (for example, if you want to concentrate on an intellectual task). It also seems to make tianeptine just "smoother" and subtler overall for me (a good thing). Maybe it competes with tianeptine by occupying or regulating the AMPA-glycine receptor? However, noopept doesn't allow me to take tianeptine regularly alongside LDN -- I still get the side effects mentioned. It's not really an option for me to stop LDN, as whenever I've tried to do so for more than two days, my chronic inflammation comes galloping back.